In reflection of modern society with its growing size of the elderly population and increasing levels of stress, opportunities for exposure to the risk of scalp hair loss due to various factors are continuing to increase, and there is an extremely high demand to compensate for hair loss accompanying aging and the like. Aesthetic or medical efforts are being made to accommodate this situation, including not only the use of hair tonic and hair restoration products, but also actual hair growth and hair transplants. Moreover, accompanying technical breakthroughs attributable to recent progress in stem cell research as well as in consideration of a serious shortage of donors due to problems with tissue compatibility along with ethical demands with respect to criteria for determination of brain death, extremely high, and perhaps somewhat excessive, expectations are being placed on regenerative medical technology as a form of advanced medicine to take the place of conventional organ transplants, resulting in a level of attention higher than ever before being placed on hair follicle regeneration as a model organ of regenerative medicine.
The mechanism of hair follicle formation in the developmental stage has research comparatively extensively, and hair follicles have been determined to be formed as a result of complex interactions between epithelial cells (epidermal cells) and mesenchymal cells lying directly there below (hair papilla cells or dermal papilla cells (DPC)) mediated by signal transduction (R. Pause, et al., N. Engl. J. Med., 341, 491-497, 1999 (Non-Patent Document 1); K. S. Stenn, et al., Physiol. Rev., 81, 449-494, 2001 (Non-Patent Document 2); S. E. Miller, et al., J. Invest. Dermatol., 118, 216-225, 2002 (Non-Patent Document 3). In addition, once formed, hair follicles are organs that undergo repeated cyclical regeneration consisting of a growth phase, transition phase and resting phase, and although numerous physiologically active substances, such as growth factors, cytokines, hormones or neuropeptides, are known to be involved in their regulation, these physiologically active substances do not necessarily coincide with those involved in the mechanism of hair follicle formation in the developmental stage.
It has been determined from mouse hair follicle reconstruction experiments using nude mice that both epithelial cells and mesenchymal cells are essential for hair follicle regeneration, and that hair follicle regeneration is not induced unless at least a fixed number of cells are present (Kishimoto, J., et al., Proc. Natl. Acad. Sci., 96, 7336-7341, 1999 (Non-Patent Document 4). Moreover, although it also been demonstrated that chimeric hair follicles composed of mouse DPC and human epithelial cells can be regenerated (Japanese Unexamined Patent Publication No. 2005-132813 (Patent Document 1); Ehama, et al., 26th Annual Conference of the Molecular Biology Society of Japan, Collection of Lecture Abstracts 2PC-024, 2003 (Non-Patent Document 5)), complete regeneration of human hair follicles has yet to be achieved. One reason for this is that it is difficult to obtain an amount of human DPC capable of inducing hair follicles that is adequate for use in transplantation.
Although cells such as DP that express versican, for example, under specific conditions have been shown to have the ability to specifically induce hair follicles (Kishimoto, J., et al., Proc. Natl. Acad. Sci., 96, 7336-7341, 1999 (Non-Patent Document 4)), the mechanism regarding induction of hair follicle formation at the molecular level remains largely unknown.
Although numerous factors are thought to be involved and function in hair growth of the hair cycle and the mechanism of hair restoration in this manner, there are also thought to be numerous proteins and expression genes thereof for which involvement is still not known, and considerable expectations are currently being placed on elucidation of the details thereof. Elucidation of the mechanisms of hair growth and hair restoration will be extremely useful in the development of methods for promoting hair follicle formation and/or regeneration and the development of drugs used for that purpose, as well as in terms of further advancement of regenerative medical technology and the like.